HIV protease inhibitors (HIV-PIs) are antiretroviral agents approved for human use since 1993. HIV-PIs are designed to bind to the catalytic site of HIV protease selectively and thus block the replication and production of infective viral particles (Decks et al 1997). It was shown that these drugs affected several important cellular processes such as angiogenesis, inflammation, processing and presentations of antigens, cell survival and tissue remodelling (Sgadari et al. 2003, Andre et al. 1998, Gruber et al. 2001, Delmonte et al. 2007). Recent evidence indicated strong anticancer capacity of HIV-PIs both in vitro and in vivo. Inhibition of growth of different tumor cells was accompanied with the induction of apoptotic cell death (Chow et al. 2006, Pajonk et al. 2002, Ikezoe et al. 2004, Ikezoe et al. 2000, Gills et al. 2007). Despite the fact that the mechanisms of action of these drugs are not strictly defined, their potential targets are: AKT, extracellular signal-regulated kinase, nuclear factor-kB, signal transducers and activators of transcription 3, matrix metalloproteinase, basic fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) (Pajonk et al. 2002, Ikezoe et al. 2004, Sgadari et al. 2002, Ikezoe et al. 2004, Gupta et al. 2005, Cuneo et al. 2007). Moreover, it was shown that these drugs sensitize tumor cells to radiation, enhance the anticancer effects of other cytostatic drugs and also inhibit growth and invasion of angiogenic tumor cells in nude mice (Ikezoe et al. 2004, Sgadari et al. 2002, Gupta et al. 2005).
Unfortunately, the application of these drugs was followed with many unpredicted and adverse effects such as hyper- or hypolipidaemia, cardiovascular diseases, diabetes, body fat redistribution, osteopenia and osteoporosis (Flexner, 1998). Addition of NO moiety is one of the current approaches employed in order to reduce toxicity and enhance drug efficacy. This type of chemical modification was applied on numerous non-steroidal anti-inflammatory drugs.